simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
Hepatitis Virus C (HVC) protease inhibitors 4812 923604-59-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • olysio
  • TMC-435
  • TMC435350
  • simeprevir
  • simeprevir sodium
Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.
  • Molecular weight: 749.94
  • Formula: C38H47N5O7S2
  • CLOGP: 5.45
  • LIPINSKI: 3
  • HAC: 12
  • HDO: 2
  • TPSA: 156.89
  • ALOGS: -5.39
  • ROTB: 7

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
May 14, 2014 EMA
Nov. 22, 2013 FDA JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 761.49 35.46 301 4414 100425 50499984
Anaemia 561.84 35.46 325 4390 252131 50348278
White blood cell count decreased 460.22 35.46 221 4494 116501 50483908
Blood bilirubin increased 380.59 35.46 134 4581 31904 50568505
Neutrophil count decreased 275.48 35.46 117 4598 45909 50554500
Haemoglobin decreased 211.83 35.46 137 4578 127079 50473330
Hyperbilirubinaemia 164.68 35.46 53 4662 9517 50590892
Haemolytic anaemia 145.84 35.46 48 4667 9244 50591165
Hepatitis C 108.72 35.46 33 4682 4884 50595525
Hepatocellular carcinoma 107.63 35.46 27 4688 1972 50598437
Pruritus 103.10 35.46 129 4586 283439 50316970
Off label use 102.17 35.46 168 4547 474258 50126151
Pyrexia 91.80 35.46 142 4573 380061 50220348
Photosensitivity reaction 84.29 35.46 35 4680 12876 50587533
Remission not achieved 52.61 35.46 9 4706 94 50600315
Decreased appetite 45.38 35.46 73 4642 200850 50399559
Hepatic failure 42.08 35.46 30 4685 32253 50568156
Hepatic function abnormal 41.75 35.46 30 4685 32651 50567758
Jaundice 40.18 35.46 27 4688 26402 50574007
Sunburn 40.04 35.46 13 4702 2390 50598019
Hepatic encephalopathy 39.93 35.46 19 4696 9617 50590792
Hepatitis C RNA increased 37.37 35.46 7 4708 126 50600283
Depressive symptom 36.39 35.46 13 4702 3187 50597222

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 543.91 28.88 300 5265 104372 29464590
White blood cell count decreased 391.23 28.88 224 5341 83138 29485824
Blood bilirubin increased 351.15 28.88 156 5409 33737 29535225
Anaemia 309.56 28.88 273 5292 200678 29368284
Hepatitis C 286.94 28.88 94 5471 8816 29560146
Hepatocellular carcinoma 254.09 28.88 81 5484 6957 29562005
Off label use 214.24 28.88 271 5294 300529 29268433
Hyperbilirubinaemia 171.31 28.88 74 5491 14860 29554102
Neutrophil count decreased 144.17 28.88 94 5471 43473 29525489
Haemoglobin decreased 143.66 28.88 136 5429 108239 29460723
Photosensitivity reaction 140.34 28.88 56 5509 9202 29559760
Drug ineffective 95.94 28.88 210 5355 362960 29206002
Jaundice 72.67 28.88 53 5512 29243 29539719
Remission not achieved 71.77 28.88 13 5552 89 29568873
Pruritus 69.47 28.88 97 5468 116752 29452210
Haemolytic anaemia 59.56 28.88 31 5534 9388 29559574
Sunburn 51.69 28.88 17 5548 1603 29567359
Treatment failure 49.93 28.88 47 5518 36892 29532070
Hepatic failure 46.27 28.88 42 5523 31470 29537492
Genotype drug resistance test positive 46.22 28.88 14 5551 1009 29567953
Pyrexia 44.99 28.88 137 5428 287485 29281477
Ascites 44.59 28.88 44 5521 36575 29532387
Viral load increased 44.02 28.88 16 5549 2033 29566929
Hepatitis C RNA increased 42.38 28.88 10 5555 274 29568688
Hepatic encephalopathy 40.27 28.88 27 5538 13008 29555954
Thought blocking 38.29 28.88 8 5557 123 29568839
Bilirubin conjugated increased 38.01 28.88 16 5549 3001 29565961
Rash 34.96 28.88 96 5469 189723 29379239
Choroiditis 34.08 28.88 11 5554 977 29567985
Hyperuricaemia 33.34 28.88 19 5546 6870 29562092

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 1351.13 29.50 600 8987 167111 64322034
White blood cell count decreased 894.43 29.50 444 9143 157393 64331752
Anaemia 846.23 29.50 581 9006 378099 64111046
Blood bilirubin increased 681.15 29.50 272 9315 57281 64431864
Neutrophil count decreased 414.02 29.50 210 9377 76986 64412159
Hepatitis C 384.83 29.50 117 9470 10898 64478247
Haemoglobin decreased 357.77 29.50 267 9320 194796 64294349
Hepatocellular carcinoma 357.69 29.50 104 9483 8299 64480846
Hyperbilirubinaemia 313.32 29.50 118 9469 21087 64468058
Haemolytic anaemia 200.18 29.50 79 9508 15974 64473171
Pruritus 156.28 29.50 211 9376 312189 64176956
Photosensitivity reaction 138.31 29.50 63 9524 18110 64471035
Pyrexia 136.87 29.50 273 9314 558371 63930774
Jaundice 105.75 29.50 74 9513 48438 64440707
Remission not achieved 104.73 29.50 21 9566 335 64488810
Off label use 103.00 29.50 263 9324 632543 63856602
Hepatic failure 81.88 29.50 67 9520 55327 64433818
Hepatic encephalopathy 65.10 29.50 40 9547 21026 64468119
Rash 62.64 29.50 179 9408 458370 64030775
Hepatitis C RNA increased 62.53 29.50 14 9573 386 64488759
Bilirubin conjugated increased 60.32 29.50 24 9563 4944 64484201
Ascites 56.20 29.50 57 9530 61944 64427201
Pain 55.92 29.50 8 9579 553503 63935642
Hyperuricaemia 55.23 29.50 28 9559 10163 64478982
Sunburn 54.48 29.50 20 9567 3312 64485833
Decreased appetite 52.97 29.50 124 9463 281165 64207980
Insomnia 48.42 29.50 97 9490 197739 64291406
Malaise 47.69 29.50 148 9439 396099 64093046
Hepatorenal syndrome 45.14 29.50 18 9569 3728 64485417
Aspartate aminotransferase increased 43.78 29.50 70 9517 119718 64369427
Red blood cell count decreased 41.15 29.50 43 9544 48343 64440802
Hepatic function abnormal 40.72 29.50 49 9538 64264 64424881
Hepatic cirrhosis 39.23 29.50 32 9555 26266 64462879
Viral load increased 37.26 29.50 14 9573 2473 64486672
Thought blocking 36.87 29.50 8 9579 190 64488955
Liver disorder 36.01 29.50 42 9545 53309 64435836
Choroiditis 35.60 29.50 11 9576 1076 64488069
Alanine aminotransferase increased 31.41 29.50 66 9521 138965 64350180
Incorrect product administration duration 31.35 29.50 19 9568 9739 64479406
Injection site dermatitis 31.23 29.50 5 9582 19 64489126

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AP05 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000182638 HCV NS3/4A Protease Inhibitors
FDA EPC N0000182639 Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000193845 Bile Salt Export Pump Inhibitors
FDA MoA N0000193960 Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA N0000193965 Sodium Taurocholate Co-transporting Polypeptide Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.35 acidic
pKa2 6.66 Basic
pKa3 3.5 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8349869 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8741926 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8754106 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9040562 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9353103 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9623022 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9856265 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8148399 Sept. 5, 2029 METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cathepsin S Enzyme IC50 6.10 CHEMBL
Hepatitis C virus serine protease, NS3/NS4A Enzyme INHIBITOR Ki 9.30 CHEMBL CHEMBL
Genome polyprotein Polyprotein INHIBITOR Ki 9.44 SCIENTIFIC LITERATURE DRUG LABEL
Nonstructural protein NS3-4A Unclassified Ki 9.44 CHEMBL
Polyprotein Polyprotein INHIBITOR Ki 9.44 IUPHAR
Genome polyprotein Unclassified Ki 9.30 CHEMBL

External reference:

IDSource
D10081 KEGG_DRUG
1241946-89-3 SECONDARY_CAS_RN
4032900 VANDF
CHEBI:134743 CHEBI
30B PDB_CHEM_ID
CHEMBL501849 ChEMBL_ID
7367 IUPHAR_LIGAND_ID
9432 INN_ID
DB06290 DRUGBANK_ID
9WS5RD66HZ UNII
24873435 PUBCHEM_CID
1482790 RXNORM
207569 MMSL
29896 MMSL
d08182 MMSL
015309 NDDF
015310 NDDF
708823009 SNOMEDCT_US
714167009 SNOMEDCT_US
D000069616 MESH_DESCRIPTOR_UI
C2605855 UMLSCUI
CHEMBL3137358 ChEMBL_ID

Pharmaceutical products:

None